Identification of ALDH18A1 as a Therapeutic Target in Type 2 Diabetes Mellitus via Integrated Bioinformatics Approaches

Type 2 diabetes mellitus (T2DM) is a multifactorial condition that is characterized by a range of physiological abnormalities leading to hyperglycemia and can lead to serious complications affecting various organs. These complications, such as cardiovascular diseases, neuropathy, nephropathy and retinopathy, significantly impact quality of life and can lead to severe outcomes if not properly managed. This study leverages publicly available genomic datasets to identify potential therapeutic targets for T2DM. We identified 215genes that were differentially expressed from three different microarray datasets obtained from the Gene Expression Omnibus database. Hub gene analysis of the protein‒protein interaction network revealed that aldehyde dehydrogenase 18 family member A1 (ALDH18A1) is a key candidate for further investigation. Molecular docking demonstrated the binding affinities of the natural compound galioside and the FDA-approved drug formoterol for ALDH18A1, with docking scores of –7.13kcal/mol and –7.21kcal/mol, respectively. These findings were further supported by drug-likeness analysis, followed by 200ns molecular dynamics (MD) simulations that confirmed the stability of the ALDH18A1-ligand complexes, indicating that these compounds could maintain effective binding under physiological conditions. Our identification of ALDH18A1 as a key molecular player in T2DM pathogenesis, coupled with the discovery that the structurally diverse compounds galioside and formoterol exhibit stable binding affinities, opens new avenues for therapeutic interventions, offering a novel dual-target strategy to modulate ALDH18A1 activity and mitigate the complications of T2DM.